From Molecular Insights to Patient Stratification for Neurological and Psychiatric Disorders Proceedings of a Workshop (2022) / Chapter Skim
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1 Introduction and Background
1 Introduction and Background
Pages 1-6
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; however, progress continues to lag for more common neurological and psychiatric disorders that are more heterogeneous, such as Parkinson's disease, Alzheimer's disease, and schizophrenia. For these disorders, critical challenges include poor mechanistic insight and a lack of biomarkers that can be used to stratify individuals within broad symptom-based diagnostic categories, which hinder progress in developing novel therapeutics based on genetic findings.
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Earlier workshops in this series addressed a range of topics related to improving therapeutic development in this field. In 2012, the Neuroscience Forum hosted a workshop titled Improving the Utility and Translation of Animal Models for Nervous System Disorders that explored the limita tions in the use of animal models, recognizing that even though they can not model human brain disorders, they are critical as models of disease mechanisms (IOM, 2013)
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• Examine the use of genetics and other technologies to facilitate identifi cation of genetic variation, understand the effects of both common and rare variants on disease-relevant function, and gain insights into disease mechanisms and molecular pathways in order to identify biomarkers that enable patient stratification to advance therapeutic development. o Consider how these steps will benefit from advanced computational approaches and "big data" produced by new technologies ranging from the molecular to neural systems level to human phenotyping.
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The problem of insufficient genetic diversity in genetic research and efforts underway to build more ancestrally diverse genomic datasets are discussed in Chapter 3. Novel approaches aimed at linking genes to causality in complex diseases are discussed in Chapter 4.
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FIGURE 1-1 A stepwise approach for developing biomarkers for patient stratification in clinical trials. NOTE: CNV = copy number variation; CSF = cerebral spinal fluid; DNA = deoxyribonucleic acid; iPS = induced pluripotent stem cells; RNA = ribonucleic acid SOURCE: Presented by Dimitri Krainc, October 5, 2021.
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